Epigenetic Reprogramming and Drug Resistance in Age-Related Cancers: From Stemness to Survivorship

Cancer incidence rises sharply with age, yet the biological mechanisms that make older patients more vulnerable to treatment failure remain poorly understood. While targeted therapies have transformed outcomes across the broader population, a substantial subset of older patients develop resistance, experience relapse, and carry a disproportionate survivorship burden. Epigenetic reprogramming has emerged as a compelling link between the biology of ageing and this therapeutic vulnerability.Ageing drives profound remodelling of the epigenome across tissue types, altering DNA methylation landscapes, histone modification states, and non-coding RNA networks in ways that reshape chromatin accessibility and rewire gene expression. These changes create fertile ground for cancer stem cell (CSC) emergence, a population increasingly recognised as the engine of tumour heterogeneity, metastatic spread, and drug resistance. Strikingly, the epigenetic hallmarks of CSC identity closely mirror those of cellular ageing itself, including senescence-associated secretory phenotype (SASP) signalling, epigenetic clock acceleration, and dysregulation of polycomb and trithorax complexes, suggesting that ageing and stemness converge on shared molecular programmes.How the aged epigenome primes tumours to resist chemotherapy, targeted therapies, and immune checkpoint blockade is a question of urgent clinical relevance across cancer types. Equally pressing are the survivorship consequences of treatment in this population, where therapy-induced epigenetic ageing compounds existing comorbidities and contributes to cognitive decline, cardiometabolic risk, and secondary malignancy.This Research Topic brings together researchers across cancer epigenetics, geroscience, stem cell biology, clinical oncology, and survivorship medicine to map the ageing-epigenome-resistance axis and translate these insights into better outcomes for older cancer patients. We welcome original research articles, systematic reviews, meta-analyses, and perspective pieces spanning basic, translational, and clinical domains.Topics of interest include, but are not limited to:1. Epigenetic clocks and cancer risk: DNA methylation age acceleration as a biomarker of susceptibility, aggressiveness, or treatment response across cancer types2. Age-associated chromatin remodelling and stemness: histone modifications (H3K27me3, H3K4me3, H3K9me2/3), chromatin remodellers (EZH2, DNMT3A/B, TET enzymes), and 3D genome organisation in driving CSC phenotypes3. Epigenetic mechanisms of drug resistance: methylation-driven silencing of tumour suppressors, enhancer reprogramming, and bivalent chromatin states underpinning resistance to chemotherapy, hormone therapies, CDK4/6 inhibitors, PARP inhibitors, and immunotherapy4. The senescence and stemness axis: how therapy-induced senescence and SASP factors fuel CSC plasticity and immune evasion5. Non-coding RNAs in ageing and resistance: lncRNA, miRNA, and circRNA networks connecting epigenetic ageing to drug-tolerant persister cell states6. Epigenetic therapies in older patients: DNMT inhibitors, HDAC inhibitors, BET bromodomain inhibitors, and combination strategies targeting epigenetic vulnerabilities across cancer types7. Survivorship and treatment-related epigenetic ageing: chemotherapy- and therapy-induced epigenetic acceleration and its consequences for cognitive function, cardiometabolic risk, and secondary cancers8. Single-cell and spatial epigenomics: high-resolution dissection of epigenetic heterogeneity within aged tumours and their microenvironments9. Liquid biopsy and epigenetic biomarkers: circulating methylation signatures, cfDNA, and exosomal non-coding RNAs for non-invasive monitoring of resistance across cancer types Topic editors: Purvi Purohit Source: https://www.frontiersin.org/research-topics/80852/epigenetic-reprogramming-and-drug-resistance-in-age-related-cancers-from-stemness-to-survivorship